Similar Datasets
Project description:IL-22 plays a critical role in defending against mucosal infections, but how IL-22 production is regulated is incompletely understood. Here, we show that mice lacking IL-33 or its receptor ST2 (IL-1RL1) were more resistant to Streptococcus pneumoniae lung infection than wild-type animals, and that single nucleotide polymorphisms in IL33 and IL1RL1 were associated with pneumococcal pneumonia in humans. The effect of IL-33 on S. pneumoniae infection was mediated by negative regulation of IL-22 production by innate lymphoid cells (ILCs), but independent of ILC2s as well as IL-4 and IL-13 signaling. Moreover, IL-33´s influence on antibacterial defense was dependent on housing conditions of the mice, and mediated by the modulatory effect of IL-33 on the intestinal microbiota. Collectively, we reveal that IL-33 controls IL-22-dependent antibacterial defense by modulating the microbiota. Our study thus provides insight into the bidirectional crosstalk between the innate immune system and the microbiota and how it shapes susceptibility to bacterial infection.
2024-03-19 | GSE236343 | GEO
Project description:IL-22 plays a critical role in defending against mucosal infections, but how IL-22 production is regulated is incompletely understood. Here, we show that mice lacking IL-33 or its receptor ST2 (IL-1RL1) were more resistant to Streptococcus pneumoniae lung infection than wild-type animals, and that single nucleotide polymorphisms in IL33 and IL1RL1 were associated with pneumococcal pneumonia in humans. The effect of IL-33 on S. pneumoniae infection was mediated by negative regulation of IL-22 production by innate lymphoid cells (ILCs), but independent of ILC2s as well as IL-4 and IL-13 signaling. Moreover, IL-33´s influence on antibacterial defense was dependent on housing conditions of the mice, and mediated by the modulatory effect of IL-33 on the intestinal microbiota. Collectively, we reveal that IL-33 controls IL-22-dependent antibacterial defense by modulating the microbiota. Our study thus provides insight into the bidirectional crosstalk between the innate immune system and the microbiota and how it shapes susceptibility to bacterial infection.
2024-03-19 | GSE236342 | GEO
Project description:IL-22 plays a critical role in defending against mucosal infections, but how IL-22 production is regulated is incompletely understood. Here, we show that mice lacking IL-33 or its receptor ST2 (IL-1RL1) were more resistant to Streptococcus pneumoniae lung infection than wild-type animals, and that single nucleotide polymorphisms in IL33 and IL1RL1 were associated with pneumococcal pneumonia in humans. The effect of IL-33 on S. pneumoniae infection was mediated by negative regulation of IL-22 production by innate lymphoid cells (ILCs), but independent of ILC2s as well as IL-4 and IL-13 signaling. Moreover, IL-33´s influence on antibacterial defense was dependent on the housing conditions of the mice, and mediated by IL-33´s modulatory effect on the intestinal microbiota. Collectively, we reveal that IL-33 controls IL-22-dependent antibacterial defense by modulating the microbiota. Our study thus provides insight into the bidirectional crosstalk between the innate immune system and the microbiota and how it shapes susceptibility to bacterial infection.
2024-03-19 | GSE236341 | GEO
Project description:IL-33 controls IL-22-dependent antibacterial defense by modulating the microbiota.
| PRJNA990658 | ENA
Project description:IL-33 controls IL-22-dependent antibacterial defense by modulating the microbiota [shotgun sequencing]
| PRJNA990667 | ENA
Project description:IL-33 controls IL-22-dependent antibacterial defense by modulating the microbiota [scRNA-seq]
| PRJNA990666 | ENA
Project description:IL-33 controls IL-22-dependent antibacterial defense by modulating the microbiota [bulk RNA-seq]
| PRJNA990664 | ENA
Project description:Host immunity limits iron availability to pathogenic bacteria, but whether immunity limits pathogenic bacteria from accessing host heme, the major source of iron in the body, remains unclear. Using Citrobacter rodentium, a mouse enteric pathogen and Escherichia coli, a major cause of sepsis in humans as models, we find that interleukin-22, a cytokine best known for its ability to promote epithelial barrier function, also suppresses the systemic growth of bacteria by limiting iron availability to the pathogen. Using an unbiased proteomic approach to understand the mechanistic basis of IL-22 dependent iron retention in the host, we have identified that IL-22 induces the production of the plasma hemoglobin scavenger haptoglobin and heme scavenger hemopexin. Moreover, the anti-microbial effect of IL-22 depends on the induction of hemopexin expression, while haptogloblin is dispensable. Impaired pathogen clearance in infected Il22-/- mice was restored by hemopexin administration and hemopexin-deficient mice had increased pathogen loads after infection. These studies reveal a previously unrecognized host defense mechanism regulated by IL-22 that relies on the induction of hemopexin to limit heme availability to bacteria leading to suppression of bacterial growth during systemic infections.
| S-EPMC5345941 | biostudies-literature
Project description:Inflammatory bowel diseases (IBD) affect over 5 million individuals in the industrialized world, with an increasing incidence rate worldwide. IBD also predisposes affected individuals to development of colorectal cancer, which is a leading cause of cancer-related deaths in adults. Mutations in genes encoding molecules in the IL-33 signaling pathway are associated with colitis and colitis-associated cancer (CAC), but how IL-33 modulates gut homeostasis is unclear. Here, we have shown that Il33-deficient mice are highly susceptible to colitis and CAC. Mechanistically, we observed that IL-33 promoted IgA production from B cells, which is important for maintaining microbial homeostasis in the intestine. Il33-deficient mice developed a dysbiotic microbiota that was characterized by increased levels of mucolytic and colitogenic bacteria. In response to chemically induced colitis, this microbial landscape promoted the release of IL-1?, which acted as a critical driver of colitis and CAC. Consequently, reconstitution of symbiotic microbiota or IL-1? ablation markedly ameliorated colitis susceptibility in Il33-deficient animals. Our results demonstrate that IL-33 promotes IgA production to maintain gut microbial homoeostasis and restrain IL-1?-dependent colitis and CAC. This study therefore highlights modulation of IL-33, IgA, IL-1?, and the microbiota as a potential therapeutic approach in the treatment of IBD and CAC.
| S-EPMC5127671 | biostudies-literature
Project description:Streptococcus pneumoniae is the most common cause of community-acquired pneumonia worldwide, and interleukin-22 (IL-22) helps contain pneumococcal burden in lungs and extrapulmonary tissues. Administration of IL-22 increases hepatic complement 3 and complement deposition on bacteria and improves phagocytosis by neutrophils. The effects of IL-22 can be tempered by a secreted natural antagonist, known as IL-22 binding protein (IL-22BP), encoded by Il22ra2 To date, the degree to which IL-22BP controls IL-22 in pulmonary infection is not well defined. Here, we show that Il22ra2 inhibits IL-22 during S. pneumoniae lung infection and that Il22ra2 deficiency favors downregulation of oxidative phosphorylation (OXPHOS) genes in an IL-22-dependent manner. Il22ra2-/- mice are more resistant to S. pneumoniae infection, have increased IL-22 in lung tissues, and sustain longer survival upon infection than control mice. Transcriptome sequencing (RNA-seq) analysis of infected Il22ra2-/- mouse lungs revealed downregulation of genes involved in OXPHOS. Downregulation of this metabolic process is necessary for increased glycolysis, a crucial step for transitioning to a proinflammatory phenotype, in particular macrophages and dendritic cells (DCs). Accordingly, we saw that macrophages from Il22ra2-/- mice displayed reduced OXPHOS gene expression upon infection with S. pneumoniae, changes that were IL-22 dependent. Furthermore, we showed that macrophages express IL-22 receptor subunit alpha-1 (IL-22Ra1) during pneumococcal infection and that Il22ra2-/- macrophages rely more on the glycolytic pathway than wild-type (WT) controls. Together, these data indicate that IL-22BP deficiency enhances IL-22 signaling in the lung, thus contributing to resistance to pneumococcal pneumonia by downregulating OXPHOS genes and increasing glycolysis in macrophages.
| S-EPMC6803344 | biostudies-literature